Background/Purpose: RA patients (pts) are at increased risk of myocardial infarction (MI) and stroke that cannot be completely explained by traditional cardiovascular (CV) risk factors. Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. Tofacitinib treatment may increase total cholesterol (TC), LDL-c and HDL-c in some pts. We evaluated major adverse CV event (MACE) risk factors in tofacitinib-treated RA pts in the clinical development program.

Methods: Data were pooled from pts with moderately to severely active RA receiving ≥1 tofacitinib dose in 6 Phase 3 and 2 long-term extension (LTE) studies (1 LTE study ongoing, data cut-off: March 2015). MACE was defined as any MI, stroke, or CV death (coronary, cerebrovascular, cardiac). Cox proportional hazard models evaluated associations between baseline (BL) values and time (BL to first tofacitinib dose) to first MACE. Changes (BL to Week [wk] 24) in MACE predictors and time to future MACE (first occurrence after 24 wks) were evaluated after adjusting for age, BL values and time-varying tofacitinib dose. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated.

Results: 52 MACE cases occurred over 12,873 pt-years (py) of exposure in 4076 pts (incidence rate: 0.4 pts with events/100 py). Table 1 shows BL characteristics for pts with/without MACE. In univariate analyses, traditional CV risk factors, corticosteroid and statin use were associated with BL MACE risk. BL disease activity and inflammation measures were not associated with MACE risk (Table 2). Increases in HDL-c (p<0.001) and decreases in TC/HDL-c ratio (p<0.05) after 24 wks of tofacitinib therapy were significantly associated with decreased risk of future MACE (Figure). In contrast, increases in ESR may be associated (p=0.09) with increased future MACE risk. Changes in TC or LDL-c or other disease activity measures were not associated with future MACE risk.

Conclusion: In pooled analyses of tofacitinib-treated pts (age and BL value adjusted), increases in HDL-c and decreases in the TC/HDL-c ratio after 24 wks of tofacitinib therapy were associated with reduced future MACE risk. Increases in ESR after 24 wks may be associated with increased future MACE risk. Increases in LDL-c and TC after 24 wks of tofacitinib therapy were not associated with future MACE risk. More data are needed to confirm these findings.